rs207459995

Variant names:

• chrM-14985-G-A
• rs207459995
• ENST00000361789.2:c.239G>A
• MT-CYB p.Arg80His

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000361789.2(MT-CYB):​c.239G>A​(p.Arg80His) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-CYB ENST00000361789.2 missense
• Scores: Apogee2 Pathogenic 0.68
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 4.44
• Publications: 6 publications found

Genes affected

MT-CYB (HGNC:7427): (mitochondrially encoded cytochrome b) Predicted to enable metal ion binding activity. Predicted to be involved in several processes, including electron transport coupled proton transport; response to cobalamin; and response to glucagon. Located in mitochondrion. Implicated in ovarian carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNE (HGNC:7479): (mitochondrially encoded tRNA glutamic acid)

TRNE Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Apogee2 supports a deletorius effect, 0.6794945 >= 0.5 .

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361789.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-CYB	ENST00000361789.2	TSL:6	c.239G>A	p.Arg80His	missense	Exon 1 of 1	ENSP00000354554.2	P00156
	MT-TE	ENST00000387459.1	TSL:6	n.-243C>T		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56387

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56387

Alfa AF: 0.0000808 Hom.: 0

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Familial colorectal cancer (1)
-	1	-	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Pathogenic	0.68
Hmtvar	Pathogenic	0.90
AlphaMissense	Benign	0.26
PhyloP100		4.4

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs207459995;

hg19: chrM-14986;